Dorzotimol (dorzolamide and timolol) eye drops solution 5 ml. vial №1

Description

Dorzotimol Storage
active substance: dorzolamide hydrochloride;

1 ml of solution contains dorzolamide hydrochloride equivalent to dorzolamide 20 mg;

Dorzotimol Excipients: benzalkonium chloride solution, citric acid anhydrous, mannitol (E 421), hypromellose, concentrated hydrochloric acid, sodium hydroxide, water for injections.

Dorzotimol Dosage form
Eye drops, solution.

Basic physical and chemical properties: transparent colorless solution.

Pharmacotherapeutic group
Antiglaucoma drugs and miotics. Carbonic anhydrase inhibitors. Dorzolamide. ATX code S01E C03.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Carbonic anhydrase (CA) is an enzyme present in many tissues of the body, including eye tissue. In the human body, carbonic anhydrase is present in the form of a number of isoenzymes, of which the most active is carbonic anhydrase-II (CA-II), present mainly in erythrocytes, as well as in other tissues. Inhibition of carbonic anhydrase in the ciliary body of the eye reduces the secretion of aqueous humor of the eye. The result is a decrease in intraocular pressure (IOP).

Dorzolamide hydrochloride contains dorzolamide hydrochloride, a potent carbonic anhydrase type II inhibitor. Following topical administration, dorzolamide reduces IOP, whether or not associated with glaucoma. Increased intraocular pressure is a major risk factor for optic nerve pathology or visual field loss. Dorzolamide does not cause pupillary constriction and reduces intraocular pressure without side effects such as night blindness, accommodation spasm. The effect of the drug on heart rate and blood pressure is minimal or absent.

Topical beta-blockers also reduce intraocular pressure, but have a different mechanism of action. Therefore, the combined use of beta-blockers with dorzolamide provides an additional reduction in IOP. These data coincide with reports of an additional effect of the combination of beta-blockers and oral carbonic anhydrase inhibitors.

Pharmacokinetics.

In contrast to oral carbonic anhydrase inhibitors, dorzolamide hydrochloride when applied topically acts directly in the eye at significantly lower doses and therefore has a less pronounced systemic effect. In clinical trials, this resulted in a decrease in intraocular pressure without concomitant acid-base imbalance or changes in electrolyte parameters, which are characteristic of oral carbonic anhydrase inhibitors.

When applied topically, dorzolamide reaches the systemic circulation. To assess the level of systemic inhibition of carbonic anhydrase in topical application of the drug was determined by the concentration of active substance and metabolites in plasma and erythrocytes, as well as the level of inhibition of carbonic anhydrase activity in erythrocytes. With long-term use, dorzolamide accumulates in erythrocytes due to selective binding to CA-II, whereas extremely low concentrations of free active substance are maintained in blood plasma. From the active substance, one N-desethylated metabolite is formed, which inhibits CA-II to a lesser extent than the parent compound, but also inhibits the less active isoenzyme CA-I. The metabolite also accumulates in erythrocytes, where it binds predominantly to CA-I. Dorzolamide is moderately bound to plasma proteins (approximately 33%) and excreted in the urine (mostly unchanged) as its metabolite. After cessation of use there is a nonlinear leaching of dorzolamide from erythrocytes, which initially leads to a rapid decrease in the concentration of the active substance, followed by a slower phase of excretion with a half-life of approximately 4 months.

When taken orally to simulate the maximum systemic effect of dorzolamide after long-term topical ophthalmic use, steady state was reached within 13 weeks. At steady state, virtually no free active substance or metabolite was detected in blood plasma; suppression of CA in erythrocytes was less than is considered necessary for pharmacological effects on renal function or respiration. Similar pharmacokinetic results were observed after long-term topical administration of dorzolamide.

However, in some elderly patients with renal insufficiency (creatinine clearance 30-60 ml / min established), the concentration of the metabolite in erythrocytes was higher, although this was not accompanied by significant differences in carbonic anhydrase inhibition; no clinically significant systemic adverse reactions directly related to these events were observed.

Indication
Treatment of high intraocular pressure in ocular hypertension or open-angle glaucoma.

Contraindication
Hypersensitivity to dorzolamide or to any of the components of the drug;
severe renal insufficiency (creatinine clearance less than 30 ml / min);
hyperchloremic acidosis.